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vaspider · 11 months

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So I'm putting this here as a sort of public service. If you have never seen a rabid animal before, and you think you can handle watching it, I think it's a good idea to watch this. It's pretty upsetting to watch, so big CW on it, because this animal is essentially "dead but still moving." This is end-stage rabies. There is no saving this animal.

Before this stage, animals may be excessively affectionate or oddly tame-looking which is part of the reason why seeing people feeding foxes is upsetting to me. These animals might be, or might become, rabid, and there's no way to know without testing, which involves destroying the animal. Encouraging wild animals to be that close to humans is generally bad.

I grew up in the woods, so unfortunately we saw an uptick in rabid animals every spring -- you'd hear there was a rabid bat in this neighborhood or a rabid fox in this one -- but as wild animals and humans cross over more and more, we will see this more and more.

Opossums and squirrels extremely rarely get rabies, and we don't know why. They think the low body temperature of opossums inhibits the virus. The most common animals which get rabies in the US are raccoons, skunks, bats and foxes. Any animal 'acting unusually' -- not skittish around humans, biting at the air or at nothing ('fly-biting'), walking strangely (they kind of look like they have a string attached to their heads and walk kind of diagonal like they're being pulled along, a lot of the time) -- should be treated as though it's potentially rabid.

If you think you have been exposed to a rabid animal, including 'waking up in a room where a bat has gotten into it and there's a fucking bat in your room', please immediately go to the emergency room. Do not pass go, do not collect $200. Post-exposure prophylaxis absolutely fucking sucks, it is a series of shots you'll have to get in two stages, it's done by weight, and it feels fucking nasty, but rabies is 100% fatal. I cannot stress enough how essential this is, having been through it.

Thank you for reading, I love everybody, the end.

#animal death #cw animal death #rabies #serious stuff #Youtube

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warandpeas · 6 months

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R.I.P.

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#costume #dog #Dog Funeral #dogs #friend #funeral #halloween #Halloween costume #mourn #mourning #Rabies #Rex

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sleeplesssmoll · 5 months

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I think Vertin might be a tactile person.

Here are examples taken from the voice lines and context clues. This isn't an all conclusive list of touchy interactions, just what I could find. Someone stop her before she gets hurt. Update: I'm going to keep adding on as we find more interactions together because this is really fun.

Sotheby (hat and hair): Stop it! You can't just touch an adult's head! (She is 13. Vertin probably sees her as a baby and pat her head).

Bette (hands): Ha ha ... They might be a little rough. To tightly grab the eave does require abundant practice. (assuming Vertin is holding her hand. Don’t ask me how we got here.)

Rabies (clothing and torso): Straws ... be hugged. Rabies ... feels it. (she hugged him 🥹)

A Knight (hat and hair): One step further, and you will be in close contact with Someone's nose... As long as you can hit Someone's head. (how close is Vertin standing to the AK? Or maybe she was looking for an invisible head to pat.)

Mesmer Jr (Hands) :Compared to the incurable anxiety, these wounds are minor. Oh, watch your distance. (smh Vertin not everyone likes being touched.)

Melania (hat and hair): "Well done. Please keep on." ...Aren't you going to say that? (more headpats but Melania needs vocal praise too.)

Lilya

Clothing and torso: Feel awesome? Now it's my turn to pet you. (...what is Vertin petting? This is clothing and torso but I'm lost.)

Hat and hair: You should be grateful that I am too lazy to move now. Or you should know that the first-class pilot’s got a first-glass head-butt, too. (Vertin taking advantage of the moment to give headpats. I'm telling you, its a THING)

Leilani (Hands): Shaka brah! Ooh! Do you want a handshake or a high-five, my friend? I'm fine with either! (She’s so wholesome)

Cristallo

hat and hair: Are you patting my head? The doctor says, this is a reward for good children. Have I done something right?

Hands and sleeves: Would you like to hold my hands? I could be with you anytime. (Cristallo is weak and frail. The nurses say she could be blown away by a gust of wind. Despite this she says she’ll be with Vertin anytime. To me it reads as Vertin being worried Cristallo will disappear too. Cristallo notices so she offers to hold hands and says she will always be here as a way to comfort her.)

Darley Clatter

Hat and Hair: Oh ... I can't deny you are really good at patting.

Clothing and Torso: Take a look at my beautiful muscles! I don't need to explain how fabulous I am. Hey, watch out! Rub me in the direction my mane grows.

Bonus Intimacy : Adorable? Ahh? You don't even have a taste! (Vertin pets him and calls him adorable. Darley, don’t let the girlies know. They might end your noble bloodline.)

Pavia (Hat and Hair): Wanna know how many holes I've made on others' heads? No? Then stop it. (What possessed her to give Pavia headpats?)

Dikke (hat and hair): Thou art overstepping my boundaries, arcanist. (I’m guessing Vertin is at it again with the headpats. Dikke smiles when she says this so she isn’t offended. If anything, she seems amused. )

Eternity (hands and sleeves): Go on, try holding it, and feel its temperature rising in your hand… Easy, sweetheart… take it easy, heh heh… (more hand holding but Vertin wasn’t prepared this time)

An-an Lee (hands and sleeves): What? You want a palm reading? (Vertin, why are you like this? Are you randomly touching people's hands?)

I feel like I should have picked up on this sooner. Gift-giving, hand holding, and headpats. This is the Timekeeper way.

Regulus (hands and sleeves): What do you want? I don't have any spare scratch. (I'm sure she knows you're broke since she's your boss. Vertin's just being Vertin at this point.

Vertin leads Regulus by the hand into her Suitcase in the prologue

Blonney (hands): Interesting! It's been a while since I last met someone who would start with holding hands.

She also holds Blonney's hand as she calms her down during the green lake event.

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undercover-omlette · 6 months

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i just fell down another gacha hell

#reverse 1999 #A Knight #APPLe #Rabies #poltergeist #reverse 1999 fanart #skyotan

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crocchompers · 1 month

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more feral beta because he deserves the spot light once again

#he's a bad kitty cat #poor thing #his rabies shots didn't help nothing he still has his rabies #he's so stupid #he's not a strong stray #but he's definitely one of the more aggressive ones #Feral Beta #Beta Wally #welcome home #wally darling #feral stray cat #rabies

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one-time-i-dreamt · 1 year

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I adopted 13 kids that I found under my old school’s playground but they all had rabies.

#dream #adoption #kids #family #school #playground #rabies

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magnetothemagnificent · 1 year

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Wonder if the idea that demons can be repelled by holy water comes from rabies.....organisms infected rabies behave erratically and violently, salivate at the mouth, all classic "symptoms" of demonic possession. But one key thing that rabies does that other pathologies don't is it causes the infected organism to be hydrophobic - react violently to water.

#disease anthropology #demonic possession #rabies

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tater-tot-jr · 2 months

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Alright whump community I’m about to blow your mind.

Rabies.

You heard me, it’s the most whumpy thing imaginable. It has no cure, only fourteen people have ever survived. It’s slow, it’s painful, and it’s perfect. It causes aggression, paranoia, a high fever, hallucinations, foaming at the mouth, and a fear of water so great people literally dehydrate to death. Imagine being a whumpee who got bit by a wild animal with no access to doctors, slowly watching yourself go insane and knowing you’re screwed. A caretaker who has to watch whumpee die in such a horrible way and no hope of them even being lucid in their final moments. A whumper putting their beloved pet down because they got bit by a raccoon.

This is my best idea ever. Intellectually, I’ve peaked.

#pet whump #whump community #whump #rabies

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excalculus · 14 days

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I saw some mentions of rabies going around again and have no clue what's set it off this time, but given recent scientific developments I want to revisit the idea of curing symptomatic rabies.

First things first: there is still no practical way to do this. The famous Milwaukee Protocol fails far more frequently than it succeeds, and even the successes are not making it out in anything like a normal state. It's been argued that it should no longer be considered a valid treatment [1] due to these issues; any continued use is because there's literally nothing else on the table.

However. There are now two separate studies showing it's possible to cure rabies in mice after the onset of symptoms. The lengths you have to go to in order to pull this off are drastic, to put it mildly, and couldn't really be adapted to humans even if you wanted to. But proof of concept is now on the board.

long post under the cut, warnings for animal experimentation and animal death. full bibliography at the end and first mention of each source links to paper.

Quick recap - rabies is a viral disease of mammals usually transmitted through the saliva of an infected animal. From a contaminated bite wound, it propagates slowly for anywhere from days to months until it reaches the central nervous system (CNS). Post-exposure vaccination can head it off during this phase, but once it reaches the CNS and neurological symptoms appear it's game over. There will typically be a prodromal phase where the animal doesn't act right - out at the wrong time of day, disoriented, abnormally friendly, etc. This will then progress to the furious (stereotypical "mad dog" disease) and/or paralytic phases, with death eventually caused by either seizures or paralysis of the muscles needed for breathing.

That's the course we're familiar with in larger animals. Mice, though, are fragile little creatures with fast metabolisms.

In the first study's rabies infection model, lab mice show rabies virus in the spinal cord by day 4 after infection and in the brain by day 5. Weight loss and slower movement start by day 7, paralysis starting from the hind limbs from day 8 on, and if not euthanized first they're dead by day 10-13. [2]

This study (fittingly conducted at the Institut Pasteur) had two human monoclonal antibodies, and wanted to see if there was any possibility they could be used to cure rabies after what we think of as the point of no return.

Injecting the antibodies into muscle saved some mice if done at days 2 or 4, and none if done later, even at high doses of 20 milligrams per kilogram of body weight of each. Conclusion: targeting the virus out in the rest of the body is no use if it's already replicating in the CNS.

Getting a drug past the blood-brain barrier is, to use a highly technical term, really fucking hard. It's the sort of problem that even the best-funded labs and biggest companies in the world routinely fail at. And that's for small molecule drugs, which are puny compared to antibodies.

But this isn't drug development for a clinical trial. This is a very, very early proof-of-concept attempt, which means you're willing to ignore practicality to see if this idea is even remotely workable. So you can do things like brute force the issue by cutting through the skull to implant a microinfusion pump, which lets you deliver the antibodies directly into the normally-protected space around the brain. Combine this with the normal injections, and you can treat both the CNS and the rest of the body at the same time. Here's a survival graph of treated mice. X axis is days, Y axis is percentage of mice in that group still alive.

Figure 2A from reference 2, accessed February 2024

The fact that the blue, green, and purple lines did anything other than sink horribly to zero is unheard of. When the combination treatment was started at day 6, 100% of the mice survived. Started at day 7 (prodromal phase), 5 out of 9 mice recovered and survived. Started at day 8 (solidly symptomatic, paralysis already starting to set in), 5 of 15 mice recovered and survived. And when they say "survived", they kept these mice all the way to day 100 to make sure. Some of them had permanent minor paralysis but largely they were back to being normal mice doing normal mouse things. So, success, but by pretty extreme means.

Enter the second paper [3]. This was a different approach using a single human monoclonal antibody against Australian bat lyssavirus (ABLV - closely related to rabies, similar symptoms in humans) to try for a cure without needing to deliver treatments directly into the CNS. They also made a luminescent version of ABLV that let them directly image viral activity, so they could see both where the virus was replicating and how much there was in a live mouse.

Figure 1 from reference 3, accessed February 2024

Mice infected with ABLV start showing symptoms around day 8. You can see in the figure that at day 3 there's viral replication in the foot at the site of infection, which has shifted into the spine and brain by day 10. So what happens if you give one of these doomed mice one single injection of the antibody into the body?

Done at day 3, the virus doesn't make it to the brain until day 14, and while disease does set in after that around 30% of the mice survive. Days 5 and 7 are much more interesting. Those mice still develop symptoms at day 8, but the imaging shows the amount of virus in their spines and brains never gets anywhere near the levels seen in untreated controls, and within days it starts to decrease. Around 80% of day 5 and 100% of day 7 mice survive.

Okay, sure, you can stop another lyssavirus, but technically you did start treatment before symptoms appeared. What about symptomatic rabies?

The rodent-adapted rabies strain CVS-11 starts causing symptoms as early as day 3 after infection, and untreated mice die between days 8 and 11. The same single dose of antibody saved 67% of mice treated on day 5 and 50% of mice treated on day 7. Without making the luminescent version of the virus there's no real-time imaging of the infection, but you can still track symptoms.

Figure 2 from reference 3, accessed February 2024. CVS-11 is the name of the rodent rabies strain and F11 is the name of the antibody.

Disease score is a combination of several metrics including things like whether the mice are behaving normally and whether they show signs of paralysis. In untreated mice it goes up and up, and then they die. If one of those lines starts coming back down and continues past day 10 or so, that's a mouse that recovered. The success rate isn't as good as against ABLV, but again, this is a rabies strain specifically adapted to rodents and treatment wasn't started until it was well-established in the CNS.

So how on earth is this happening? The antibody neutralizes both ABLV and rabies really well in a test tube, but we've already established that there's no way a huge lumbering antibody is making it past the blood-brain barrier without serious help. Something about the immune response is clearly making it in there though. And it turns out that if you start trying this cure in mice missing various parts of their immune systems, mice without CD4+ T cells don't survive even with the treatment. By contrast mice without CD8+ T cells take longer to work through the infection, but they eventually manage it and are immune to reinfection afterwards.

To grossly oversimplify the immune system here, CD4+ are mature helper T cells, which work mostly by activating other immune cells like macrophages (white blood cells) and CD8+ T cells (killer T cells) against a threat.

Normally, T cells are also kept out by the blood-brain barrier, but we know that in certain specific cases including viral infection they can pass it to migrate into the brain. In the brains of the infected mice for which antibody treatment either wasn't given or didn't work, you can find a roughly even mix of CD8+ and CD4+ T cells along with a whole lot of viral RNA. But in the brains of those successfully fighting off the infection, there's less viral RNA and the cells are almost exclusively CD4+. So the antibody doesn't work by neutralizing the virus directly - something about it is activating the animal's own immune system in a way that gives it a fighting chance.

Again, neither of these proof of concept treatments is really workable yet as a real world cure. The first one is almost hilariously overkill and still has a pretty good chance of failure. The second is less invasive but careful sequencing still shows both low-level viral replication and signs of immune response in the brains of the survivors even at day 139, so it may not be truly clearing the virus so much as trading a death sentence for life with a low-level chronic infection. But now we know that 1. curing rabies after symptoms begin is at least theoretically possible, and 2. we have some clues as to mechanisms to investigate further.

Not today. Not tomorrow. But maybe not never, either.

References:

Zeiler, F. A., & Jackson, A. C. (2016). Critical appraisal of the Milwaukee protocol for rabies: this failed approach should be abandoned. Canadian Journal of Neurological Sciences, 43(1), 44-51.

de Melo, G. D., Sonthonnax, F., Lepousez, G., Jouvion, G., Minola, A., Zatta, F., ... & Bourhy, H. (2020). A combination of two human monoclonal antibodies cures symptomatic rabies. EMBO molecular medicine, 12(11), e12628.

Mastraccio, K. E., Huaman, C., Coggins, S. A. A., Clouse, C., Rader, M., Yan, L., ... & Schaefer, B. C. (2023). mAb therapy controls CNS‐resident lyssavirus infection via a CD4 T cell‐dependent mechanism. EMBO Molecular Medicine, 15(10), e16394.

#rabies #biology #long post #animal death #medicine #original content

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